In this COBRE, novel approaches to developing chemical probes and therapeutic leads will be pursued by a diverse team of scientists. This COBRE will create new libraries for high-throughput screening, provide new perspectives on innate immune response and neurodegenerative disease, enable new screening technology, and advance the state of the art in virtual screening. The proposed COBRE will build a network of scientific collaboration throughout the UD campus through five subprojects: 1. Development of an Immunostimulatory Small Molecule Library 2. In vitro neural disease models for high throughput drug screening 3. New Synthetic Methods for Diverse Small Molecule Library Preparation 4. Electrochemical Chemiluminescent Arrays and Emitters for Rapid Chemical Probe Identification 5. Realizing the predictive promise of high throughput virtual screening The proposed COBRE will establish a regional network of biomedical collaboration between scientists at UD and the Nemours Center for Childhood Cancer Research. In a rich collaboration across all five subprojects, UD researchers will interface extensively with scientists from the NCI Molecular Targets Laboratory (MTL) and Chemical Biology Laboratories (CBL), with interactions that include mentorship by NCI scientists, crosstraining experiences for graduate students at NCI, and collaborative mechanisms for follow-up on promising discoveries. With new core instrumentation and facilities, this COBRE will increase the infrastructure for biomedical research at UD. The scope of the center will be further expanded through faculty recruitment and seed grants, and via explicit mechanisms that will facilitate both biological and chemical follow-up on initial discoveries. This COBRE will also establish a mentoring network that will support the career development of assistant faculty, and place them on an accelerated path toward independent funding.